The aryl-, heteroaryl- or alkenyl-substituted unsaturated hydrocarbons are useful as a physiological active substance (e.g., medicine, agrichemical), a functional material (e.g., liquid crystal material, electronic material, optical material, photographic additive, thermosetting resin), or a synthetic intermediate thereof (see, for example, Patent Documents 6 to 9).
The aryl- or alkenyl-substituted unsaturated hydrocarbons are obtained, for example, by reacting aryl halides or alkenyl halides with alkynes or alkenes in the presence of a palladium catalyst (so-called Sonogashira coupling or Mizoroki-Heck reaction).
As for the production method of aryl- or alkenyl-substituted unsaturated hydrocarbons by Sonogashira coupling, a large number of proposals have been made. For example, Patent Document 1 discloses a method of reacting an aromatic halide and an acetylene compound in the presence of a palladium catalyst, a copper salt, a base and a compound capable of releasing a halogen ion, subsequently adding dilute hydrochloric acid and an organic solvent to effect liquid separation, and purifying the organic phase by silica gel column chromatography to produce an aromatic acetylene compound.
Patent Document 2 discloses a method of performing a coupling reaction of alkynes having a methine group at the terminal and an organic compound having a leaving group such as halogen group in the presence of a catalyst containing a transition metal element such as palladium, an inorganic salt, and a ligand such as triarylphosphine or iminophosphine compound, subsequently separating the product from the reaction mixture by using high-performance liquid chromatography for sampling, and purifying the product by using gel permeation chromatography to obtain the objective coupling reaction product.
In the production methods described in Patent Documents 1 and 2, purification by extraction and chromatography is employed, but chromatography is unsuited for mass production.
Patent Document 3 discloses a production method of phenylalkynes, comprising steps of reacting a halophenol and an acetylene compound in the presence of an amine solvent, a palladium complex catalyst and a copper salt, adding dilute hydrochloric acid to the obtained reaction mixture to effect liquid separation and remove hydrogen chloride, subsequently adding an amino compound capable of forming a complex with palladium and copper, and removing the produced palladium complex and copper complex. Patent Document 5 discloses a method for synthesizing an acetylene compound having a nitrogen-containing aromatic group by a reaction of ethynylpyridines and haloaryls in the presence of a palladium catalyst and a copper catalyst. In the production methods described in Patent Documents 3 and 5, extraction for purification is employed.
Patent Document 4 discloses a method for producing an arylalkyne compound by reacting an aryl halide such as iodotoluene with an amino group-containing acetylene compound such as N-(2-propynyl)piperidine in the presence of a palladium catalyst, a base and a copper(I) salt, subsequently removing the solvent under reduced pressure, washing the residue, and finally performing distillative purification. In the production method described in Patent Document 4, distillation for purification is employed.